Replacement therapy for alpha-1-protease inhibitor deficiency in PiZ subjects with chronic obstructive lung disease

In a six-month multicenter feasibility and safety study, 20 patients, who all had a congenital deficiency of alpha-1-protease inhibitor (A1PI) of the PiZ phenotype accompanied by a chronic obstructive lung disease, were treated with human-plasma-derived A1PI. A weekly dose of 60 mg/kg, administered...

Full description

Saved in:

Bibliographic Details
Published in:	The American journal of medicine Vol. 84; no. 6A; p. 63
Main Authors:	Schmidt, E W, Rasche, B, Ulmer, W T, Konietzko, N, Becker, M, Fallise, J P, Lorenz, J, Ferlinz, R
Format:	Journal Article
Language:	English
Published:	United States 24-06-1988
Subjects:	Adult Aged alpha 1-Antitrypsin Deficiency Blood Proteins - deficiency Blood Proteins - therapeutic use Clinical Trials as Topic Female Humans Infusions, Intravenous Lung Diseases, Obstructive - drug therapy Lung Diseases, Obstructive - genetics Lung Volume Measurements Male Middle Aged Pancreatic Elastase - analysis Phenotype
Online Access:	Get more information
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	In a six-month multicenter feasibility and safety study, 20 patients, who all had a congenital deficiency of alpha-1-protease inhibitor (A1PI) of the PiZ phenotype accompanied by a chronic obstructive lung disease, were treated with human-plasma-derived A1PI. A weekly dose of 60 mg/kg, administered intravenously, was shown to be sufficient to maintain patient serum levels above the threshold limit of 35 percent, the serum level of healthy persons of the MZ phenotype. This is supposed to be the minimal effective level for protection against the elastolytic attack of the lung and, therefore, satisfies one of the most important criteria of feasibility of long-term replacement therapy. The global concentration in serum or bronchiolar lavage fluid A1PI including active and inactivated A1PI was measured immunologically by rate nephelometry and radial immunodiffusion. The functional activity of A1PI, expressed as free inhibitor activity against trypsin and leukocyte elastase, confirmed that the infused A1PI remained mostly in its active form in the circulation. Reported adverse reactions were moderate and did not require alteration to the schedule of the infusions and/or the dose and rate of administration. Antibodies to A1PI as measured by the Ouchterlony method did not develop. Laboratory and physical signs of possible hepatitis virus contamination were not observed. The long-term replacement therapy, therefore, appears to be safe.
ISSN:	0002-9343
DOI:	10.1016/0002-9343(88)90160-X